Fibroblast Injection for Amputation Healing

Overseen By Ruizhi Wang, MPhil

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Immunosuppressants, Topical steroids, Sulfonamides, others

Disqualifiers: Autoimmune conditions, Metastatic cancer, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 month

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment to improve skin healing at the site of a below-the-knee amputation. Researchers are testing whether injections of special skin cells called volar fibroblasts (autologous skin fibroblasts) can thicken and strengthen the skin at the stump site. Participants receive either the fibroblast treatment or a placebo (inactive substance) to determine which is more effective. Individuals who have had a below-the-knee amputation and currently use a prosthetic might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on chronic immunosuppressive therapies and certain other medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that injecting special skin cells from the palm or sole is safe for healthy adults. These cells aid in skin healing and may increase thickness, potentially benefiting individuals with amputations. Earlier studies reported no serious side effects, indicating that the treatment is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for amputation healing, which often involve wound care and surgical interventions, the use of autologous skin fibroblasts is unique because it harnesses the body's own cells to promote healing. This treatment involves injecting fibroblasts, a type of cell that plays a critical role in wound healing and tissue repair, directly into the amputation site. Researchers are excited about this approach because it could potentially speed up the healing process by directly enhancing tissue regeneration, offering a more natural and potentially more effective alternative to traditional methods.

What evidence suggests that autologous skin fibroblast injections might be an effective treatment for amputation healing?

Research has shown that injections using skin cells from the palm or sole, known as autologous skin fibroblasts, can thicken the skin at amputation sites. In this trial, some participants will receive these injections. Studies have found that these injections make the outer layer of skin thicker, firmer, and stronger. After treatment, reports indicate larger skin cells and longer collagen fibers. These changes might improve skin health and strength at the stump site, potentially aiding in better healing and comfort for people with amputations. ^{1 2 3 4 6}

Who Is on the Research Team?

Luis Garza, MD, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with below-knee amputations who use a prosthetic. Women must not be pregnant, breastfeeding, or planning to become pregnant and agree to contraception. Excluded are those with deep skin erosions, certain medical conditions (like autoimmune diseases), allergies to study materials, active infections, recent neuromas, or on immunosuppressives.

Inclusion Criteria

I have had an amputation below the knee.

I have been using a prosthetic for at least 3 months or had one integrated into my bone for 1 month.

I am either male or female.

Exclusion Criteria

I have dead tissue on my amputation site or slow blood return in the skin.

I am not on long-term immunosuppressive treatments, including oral or topical steroids.

You have taken any experimental medication within the last month before joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous volar fibroblast injections at the stump site to assess safety and efficacy in increasing epidermal thickness and skin firmness

1 month

Multiple visits for injections and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of skin breakdown and quality of life

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Skin Fibroblasts
• Placebo

Trial Overview The trial tests autologous volar fibroblast injections versus placebo in thickening the stump's skin layer for amputees. Participants will receive either their own cultured skin cells or a placebo injected into the stump site at Johns Hopkins.

How Is the Trial Designed?

Group I: Autologous skin fibroblasts Experimental Treatment 1 Intervention

For whole stump participants: The investigators will be comparing whole stump injection sites that receive autologous skin fibroblasts to vehicle (placebo) injections. This subject receives autologous skin fibroblast whole stump injections. For localized injection participants: The investigators are comparing two injection sites in the same individual. This site receives autologous skin fibroblasts.

Group II: Control Placebo Group 1 Intervention

For whole stump participants: The investigators will be comparing whole stump injection sites that receive autologous skin fibroblasts to vehicle (placebo) injections. This subject receives vehicle (placebo) whole stump injections. For localized injection participants: The investigators are comparing two injection sites in the same individual. This site receives a placebo.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Maryland Stem Cell Research Fund

Collaborator

Trials

1

Recruited

1+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

A patient with diabetes and severe wound complications healed a large (103.49 cm²) wound using a two-stage autologous skin substitute technique, demonstrating the efficacy of this novel approach.

The wound completely healed within 60 days after the first application of cultured fibroblasts, and after 16 months, there was no recurrence, allowing the patient to walk independently, highlighting the potential of this technique for improving wound healing in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using hyaluronic acid derivatives and cultured autologous fibroblasts and keratinocytes in a lower limb wound in a patient with diabetes: a case report. Dalla Paola, L., Cogo, A., Deanesi, W., et al.[2004]

The study involved 19 patients who received autologous cultured skin fibroblast injections to treat depressed facial skin defects, showing significant improvement in skin appearance after treatment.

The procedure was found to be safe, with only minor adverse events reported, and no serious complications or excessive cell proliferation, indicating that this method could be a reliable option for facial skin rejuvenation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary clinical observations on autologous cultured skin fibroblasts transplantation to treat the facial soft tissue deficiencies]. Zeng, W., Wei, ZR., Liu, D., et al.[2013]

In a study involving 20 patients aged 37-61, autologous dermal fibroblasts were successfully used for facial soft tissue augmentation, leading to significant and sustained clinical improvements in facial rhytides and atrophic scars.

The fibroblasts used were functionally active, producing large amounts of type I collagen, and showed no oncogenic properties or tumor formation in animal models, indicating a safe profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of injectable autologous human fibroblasts. Keller, G., Sebastian, J., Lacombe, U., et al.[2019]

Cultured autologous fibroblasts (Isolagen) have been effectively used in 1,450 patients to treat various skin issues, showing a high patient satisfaction rate of 92% regarding the correction of skin conditions after treatment.

Long-term follow-up (36 to 48 months) indicated that 70% of patients experienced continued improvement beyond the initial results, suggesting that this injectable system not only provides immediate correction but also promotes ongoing skin repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous cultured fibroblasts: a protein repair system. Boss, WK., Usal, H., Fodor, PB., et al.[2022]

Autologous fibroblast transplantation is a safe and effective method for improving atrophic scars caused by cutaneous leishmaniasis, with no observed side effects in the study.

The treatment led to significant improvements in epidermal thickness, melanin levels, and skin elasticity after two injections, although dermal thickness did not show improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fibroblast transplantation in the healing of cutaneous leishmaniasis scar: A case report. Faghihi, F., Larijani, G., Mohebbi, L., et al.[2023]

In a study involving five diabetic patients with long-standing skin ulcers, autologous skin cell implants (fibroblasts and keratinocytes) led to complete healing in 83.3% of ulcers within 21 to 120 days, demonstrating significant efficacy for difficult-to-heal diabetic ulcers.

The treatment was safe, with no adverse reactions reported, and it is a minimally invasive procedure that can be performed in an outpatient setting, making it a promising option for patients unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue therapy with autologous dermal and epidermal culture cells for diabetic foot ulcers. Marcelo, D., Beatriz, PM., Jussara, R., et al.[2018]

In a study using a porcine model of delayed wound healing, both autologous fibroblasts and keratinocytes significantly improved the re-epithelialization rates of diabetic skin wounds, achieving rates of 86.75% and 91.3%, respectively, compared to only 56.8% in saline-treated wounds.

This research suggests that while fibroblast suspensions have shown limited effectiveness in non-diabetic wounds, they can be beneficial for enhancing healing in diabetic wounds, indicating a potential new treatment strategy for diabetic skin injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell suspensions of autologous keratinocytes or autologous fibroblasts accelerate the healing of full thickness skin wounds in a diabetic porcine wound healing model. Velander, P., Theopold, C., Bleiziffer, O., et al.[2009]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/63733?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Autologous Volar Fibroblast Injection Into the Stump Site... The objective of this study is to determine if fibroblast (from palm or sole) injections are safe and effective at increasing epidermal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11457755/

The use of ectopic volar fibroblasts to modify skin identity These features included increased skin firmness, greater epidermal thickness, larger keratinocyte size, longer dermal collagen fiber length, ...

3. withpower.com withpower.com/trial/phase-3-8-2019-b4baf

Fibroblast Injection for Amputation Healing This study is a clinical trial testing the safety and efficacy of volar fibroblast (skin cells from the palm or sole) injections for thickening the ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT03947450?keyword=%22Skin%20Wound%22

Autologous Volar Fibroblast Injection Into the Stump Site of ... ~The objective of this study is to determine if fibroblast (from palm or sole) injections are safe and effective at increasing epidermal thickness and skin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01964859

Feasibility Study for Fibroblast Autologous Skin Grafts | ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4057739/

Alteration of Skin Properties with Autologous Dermal ... We outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous ...